摘要:

BackgroundTreatment of essential hypertensive patients with an AT1angiotensin receptor antagonist has previously resulted in correction of resistance artery structure and endothelial function, whereas in a parallel group treated with the beta-blocker atenolol there was no improvement of altered vascular structure and function. To test the hypothesis that patients previously treated with atenolol could present improvement of vascular structure and endothelial function if they were subjected to blockade of the renin–angiotensin system, we crossed over hypertensive patients that had been randomized to treatment with the beta-blocker atenolol to treatment with the AT1antagonist irbesartan, and studied small artery structure and endothelial function before and after treatment.MethodsEleven essential hypertensive patients (51±2 years, range 38–65; 75% male) that had previously been randomized to treatment with atenolol and treated for 1 year with good blood pressure control, were crossed over to treatment with the AT1antagonist irbesartan for 1 year. Small resistance arteries were dissected from gluteal subcutaneous biopsies that were performed before and after 1 year of treatment. The structure and endothelial function of the resistance arteries were studied on a pressurized myograph.ResultsBlood pressure control (129±3.3/85±1.8 mmHg) was identical to that achieved previously with atenolol (131±3.3/84±1.1 mmHg). Following 1 year of treatment, the arterial media width to lumen ratio (M/L) of resistance arteries (lumen diameter, 150–350 μm), which had remained unchanged under atenolol treatment, decreased from 8.44±0.45% when patients were on atenolol, to 6.46±0.30%,P<0.01, when patients received irbesartan. Maximal acetylcholine-induced endothelium-dependent relaxation was 81.1±4.1% when patients were on atenolol, unchanged from before starting treatment with the beta-blocker, and was normalized by irbesartan (to 94.8±2.0%,P<0.01).ConclusionCrossing over essential hypertensive patients with well-controlled blood pressure from the beta-blocker atenolol to the AT1receptor antagonist irbesartan resulted in correction of previously persistently altered vascular structure and endothelial function, suggesting a structural and endothelial vascular protective effect of antihypertensive treatment with the AT1receptor antagonist.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveArterial distensibility is reduced in end-stage renal failure and also after renal transplantation. The aim of the present study was to test the hypothesis that reduced carotid artery distensibility is a predictor of cardiovascular disease in patients after renal transplantation.Subjects and methodsSixty-eight asymptomatic renal transplant recipients were studied between March 1990 and December 1992, 3–6 months after transplantation. The mean duration of follow-up was 95±2 months (mean±SEM). At entry, vessel wall movements of the common carotid artery were recorded using a pulsed multigate Doppler system; blood pressure was measured by sphygmomanometry.ResultsNineteen cardiovascular events (CVE) occurred during follow-up, leading to death in six cases. The distensibility coefficient of the common carotid artery was significantly lower in patients with CVE than in those without CVE (12.2±1.0 10−3/kPa versus 16.8±0.7 10−3/kPa,P<0.005). Logistic regression analysis showed that the occurrence of cardiovascular disease during follow-up was related to carotid artery distensibility (P<0.05), independent of sex, age, smoking habits, carotid artery end-diastolic diameter, systolic and diastolic blood pressure levels, heart rate, serum creatinine, cholesterol and haemoglobin levels. Patients with a distensibility coefficient above the age-adjusted mean had a significantly longer interval free of cardiovascular disease than patients with a distensibility coefficient below the age-adjusted mean (P<0.01).ConclusionsThe distensibility of the common carotid artery is an independent predictor of cardiovascular disease in renal transplant recipients.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveIt has been suggested that non-invasive aortic stiffness measurements can be used as an indicator of atherosclerosis. The relationships of arterial stiffness with arterial wall hypertrophy and atherosclerosis however, have rarely been investigated in large-scale studies. The present study reports the associations of carotid arterial structure assessed by B-mode ultrasound with carotid-femoral pulse-wave velocity in hypertensive and non-hypertensive subjects.Design and methodsFree health examinations were performed on 564 subjects (age 58.2±10.8 years, 31.9% of women, 53.2% of all were hypertensive). Carotid–femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid ultrasound examination included measurements (at sites free of plaques) of intima–media thickness (IMT) at the common carotid arteries (CCA), CCA-lumen diameter, and assessment of atherosclerotic plaques in the extracranial carotid arteries.ResultsSubjects with carotid plaques had significantly higher mean sex-adjusted values of PWV than those without carotid plaques (12.7±0.2 versus 11.1±0.1 m/s,P<0.001). Multivariate analyses showed that this association was independent of sex, age, height, body mass index, mean blood pressure, pulse pressure, diabetes, hypercholesterolaemia and smoking habits (P<0.009). PWV was positively associated with CCA-IMT and CCA-lumen diameter in sex-adjusted analysis (partial correlation coefficients (r) were respectively 0.39 and 0.42,P<0.001 for each). However, the association of PWV with CCA-IMT, but not that with CCA-lumen diameter, disappeared after further adjustment for age and blood pressure measurements (mean blood pressure and/or pulse pressure).ConclusionThis study shows that there is a differential association of PWV with CCA-IMT and carotid plaques. The nature of the independent positive association between atherosclerosis and arterial stiffness should be thoroughly investigated.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivesIt has been recently shown that calcium channel blockers (CCBs) could also control smooth muscle cell (SMC) growth/reactivity through mechanisms that were unrelated to their CCB property. Here, we investigated the effects of amlodipine and isradipine on Ca2+movements and p42/p44 mitogen-activated protein kinase (ERK 1/2) activities, which are two early signalling events triggered by growth factors such as thrombin and basic fibroblast growth factor (bFGF).MethodsIn cultured human SMCs isolated from internal mammary arteries, Ca2+movements and ERK 1/2 activation were studied by measurement of the intracellular Ca2+concentration in Fura 2-labelled SMCs and by Western blots, respectively.ResultsIn thrombin- and thapsigargin-stimulated SMCs, amlodipine and not isradipine dose-dependently reduced Ca2+mobilization (i.e. Ca2+release from internal stores); these dihydropyridines did not affect either Ca2+influx or ERK 1/2 activation. In bFGF-stimulated SMCs, amlodipine and isradipine reduced both Ca2+influx and ERK 1/2 activation without affecting Ca2+mobilization. ERK 1/2 activation could also be directly stimulated by the l-type channel agonist Bay K 8644, demonstrating the involvement of voltage-gated Ca2+influx in this process. Most of the observed effects described were obtained with approximately 10 nmol/l amlodipine/isradipine (i.e. concentrations close to the peak plasma level in treated patients).ConclusionsIn human SMCs, amlodipine can (i) specifically alter Ca2+mobilization, likely by interacting with the sarcoplasmic reticulum and (ii) inhibit voltage-dependent Ca2+influx and the resulting ERK 1/2 activation. It is likely that amlodipine exerts its growth-inhibitory potency by interfering with multiple branches of mitogenic signalling pathways.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveSympathetic nervous and renin–angiotensin systems play important roles in essential hypertension. This study was aimed at assessing the effects of losartan or its combination with quinapril on the cardiac nervous system and neurohormonal status in essential hypertension.Design and methodsRandomized, comparative study of 105 patients with mild essential hypertension, carried out at Shizuoka General Hospital. In phase 1, 40 hypertensives were allocated randomly into the losartan (50 mg) group or the quinapril (10 mg) group. In phase 2, 65 hypertensives, after 3 months 10 mg quinapril monotherapy, were allocated randomly into groups with 50 mg losartan (n= 32) or 5 mg amlodipine (n= 33) added to quinapril, and were treated for a further 3 months. All patients underwent [123I]metaiodobenzylguanidine (MIBG) imaging and neurohormonal measurements before and 3 months after treatment.ResultsBoth monotherapies significantly increased renin activity, while losartan monotherapy also increased angiotensin II (AII) concentration. In both the losartan and quinapril groups, the washout rate was significantly decreased (18.1±11.4 versus 13.9±11.0%,P<0.0002 and 13.3±9.3 versus 12.3±9.1%,P<00001, respectively) without changes in the heart to mediastinum ratio (H/M ratio). Both combined therapies lowered blood pressure to similar levels. A combination therapy with losartan and quinapril significantly increased the H/M ratio (1.93±0.29 and 2.02±0.29,P<0.01) and decreased the washout rate (17.6±11.0 and 15.3±9.2%,P<0.02) without affecting AII concentration, whereas a combination therapy with amlodipine and quinapril therapy did not affect the scintigraphic parameters with an increase in the AII concentration.ConclusionsWith a usual antihypertensive dose, both losartan and quinapril had a little suppressive effect on the cardiac sympathetic activity in essential hypertension. In contrast, the combination therapy with losartan and quinapril, which results in a higher degree of inhibition of the renin–angiotensin system, could suppress the cardiac sympathetic activity effectively.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveSympathetic nerve activity is increased in hypertensive patients with renal artery stenosis. Less is known about cardiac vagal function in these patients before and after renal angioplasty. The aim of the present study was to investigate cardiac baroreceptor reflex sensitivity together with total body noradrenaline (NA) spillover in hypertensive patients with renal artery stenosis before, and in some patients, 1 year after renal angioplasty.Material and methodsSpontaneous baroreceptor reflex sensitivity and total body noradrenaline (NA) spillover were measured in patients with renovascular hypertension before intervention (n= 18), patients being cured/improved 1 year after renal angioplasty (n= 5) and age-matched healthy subjects (n= 25).ResultsHypertensive patients with renal artery stenosis had higher total body NA spillover (4630±619 versus 3132±210 pmol/min,P<0.05) and reduced cardiac baroreceptor reflex sensitivity (6.1±1.0 versus 10.7±1.0 ms/mmHg,P<0.01) compared with healthy subjects. Similar results were obtained (before intervention) in a subgroup of patients (n= 9) with renovascular hypertension defined as cured/improved 1 year following renal angioplasty. Baroreceptor reflex sensitivity improved after renal angioplasty in a subset of patients showing good blood pressure control 1 year after intervention (6.4±0.7 to 9.4±1.7 ms/mmHg,P<0.05).ConclusionsPatients with renovascular hypertension showed reduced cardiac baroreceptor reflex sensitivity and increased noradrenergic activity, which to some extent was reversed 1 year following successful renal angioplasty.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveAn increased sensitivity to angiotensin II (Ang II) has been observed in patients with established hypertension. In the current study we tested whether young normotensive subjects with positive family history of arterial hypertension exhibit an increased sensitivity to Ang II, thereby potentially contributing to the pathogenesis of essential hypertension in these subjects.Methods and designNormotensive young men (25±2 years) with positive family history (PFH) (n= 28) and negative family history (NFH) (n= 60) of arterial hypertension were investigated to study aldosterone response, and systemic and renal haemodynamic changes (p-aminohippurate- and inulin-clearance) to Ang II infusion (0.5 and 3.0 ng/min per kg). In addition, aldosterone response to salt loading (5 g/day for 1 week) was analysed.ResultsAmbulatory blood pressure (ABP) (mean: 84±4 versus 83±4 mmHg; NS), body mass index (23.5±2.5 versus 24.1±2.4 kg/m2; NS), and urinary sodium excretion (191±55 versus 170±73 mmol/24 h; NS) did not differ between PFH and NFH at baseline. Changes in BP, urinary sodium and potassium excretion were similar between PFH and NFH in response to salt loading. However, salt loading did not result in an adequate suppression of aldosterone in PFH compared with NFH (8±62 versus −32±39 pg/ml;P<0.001). Baseline values and changes in mean arterial BP (NFH: +13.4±7.6; PFH: +14.4±5.3 mmHg; NS), renal plasma flow (NFH: – 113±68; PFH: – 122±64 ml/min; NS) and glomerular filtration rate (NFH: +5.0±5.3; PFH: +4.2±8.3 ml/min; NS) in response to Ang II (3.0 ng/min per kg) were similar between the two groups. In contrast, the increases in serum aldosterone (PFH: 63.6±70.1 versus NFH: 37.7±46.8 pg/ml;P<0.05) and urinary potassium excretion (PFH: 0.05±0.1 versus NFH: −0.01±0.07 mmol/min;P<0.05) 30 min after stopping Ang II infusion were more pronounced and prolonged in PFH than in NFH.ConclusionsOur findings suggest that young normotensive subjects with parental history of arterial hypertension are characterized by an inadequate suppression of aldosterone production in response to salt loading and an exaggerated and prolonged hyper-responsiveness of aldosterone secretion in response to Ang II. This might contribute to the increased risk for the development of essential hypertension in subjects with positive family history of arterial hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundLimitation of systemic and glomerular hypertension reduces urinary protein excretion and prevents renal function deterioration.ObjectiveTo investigate whether, in hypertensive patients with glomerulonephritis, a combination of an angiotensin converting enzyme inhibitor (ACEI, fosinopril 20 mg/day) with an angiotensin receptor blocker (ARB, irbesartan 150 mg/day) produces a more profound antiproteinuric effect than either drug alone.MethodsTen non-diabetic patients with glomerulonephritis, normal or slightly reduced but stable renal function (creatinine clearance 40–106 ml/min) without immunosuppression were studied. Clinical evaluations, 24 h blood pressure measurements and laboratory tests were performed as follows: (1) without medication (baseline) and in random sequence; (2) ACEI alone; (3) ARB alone; and (4) combination of ACEI + ARB. Each period lasted for 6 weeks, separated by three washout periods of 4 weeks each without therapy.ResultsACEI and ARB alone reduced proteinuria from 7.9±7.1 to 5.3±5.2 and 5.0±4.9 g/24 h (mean±SD), respectively. The combination of ACEI + ARB induced a more remarkable reduction of proteinuria in every patient (to 3.3±3.7 g/24 h) than either drug alone (P= 0.039 by ANOVA). The enhanced antiproteinuric effect of the combined therapy could not be attributed to a more pronounced reduction of 24 h mean arterial pressure (basal, 106±8; ACEI, 97±5; ARB, 98±5; ACEI+ARB, 95±5 mmHg) or creatinine clearance (basal, 77±27; ACEI, 73±31; ARB 80±30; ACEI + ARB, 73±32 ml/min).ConclusionsA combination of ACEI and ARB in patients with glomerulonephritis produces a more profound decrease in proteinuria than either drug alone. This additive antiproteinuric effect is not dependent on changes in blood pressure or creatinine clearance. A long-term controlled study is required to confirm the positive effect of this treatment on the progression of renal function loss.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivesWe investigated whether arterial pressure in spontaneously hypertensive rats (SHR) can be normalized by a kidney graft from normotensive histocompatible donors. In addition, the effect of differential genetic predisposition to hypertension of recipients of an SHR kidney on the development of post-transplantation hypertension was studied.MethodsSHR were transplanted with a kidney from congenic rats (BB.1K) homozygous for a 2 cM segment of SHR chromosome 20, including the major histocompatibility complex class Ia and class II genes. BB.1K and F1 hybrids (F1H, SHR×Wistar–Kyoto rats) were transplanted with an SHR kidney and the development of renal post-transplantation hypertension was monitored.ResultsThirty days after renal transplantation, mean arterial pressure (MAP) was 116±4 mmHg in SHR with a BB.1K kidney (n= 8) versus 168±2 mmHg in sham-operated SHR (n= 10);P<0.001. Cumulative renal sodium balance (mmol/100 g body weight) over 21 days after bilateral nephrectomy was 6.8±0.6 in SHR with a BB.1K kidney versus 10.8±1.6 in sham-operated SHR (P<0.05). Within 60 days of transplantation, MAP increased in BB.1K and in F1H transplanted with an SHR kidney (n= 7 per group) by 38±5 mmHg and 43±8 mmHg, respectively.ConclusionsIn SHR, arterial pressure can be normalized by a kidney graft from normotensive donors. The genetic predisposition of the recipients to hypertension does not modify the rate and the extent of the arterial pressure rise induced by an SHR kidney graft.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivesAngiotensin II, in addition to having vasopressor effects, induces proteinuria in experimental models. Proteinuria has been reported, sometimes in the nephrotic range, in patients with chronic complete renal artery occlusion. We aimed to identify the factors associated with proteinuria in such cases.Design and main outcome measureComplete renal artery occlusion was detected by intra-arterial angiography in 96 patients referred for hypertension. We analysed patient characteristics at presentation to identify the factors associated with proteinuria.SettingA referral hypertension unit.ResultsMedian protein excretion was 0.25 g/day (range 0–11). Nine patients had nephrotic syndrome (proteinuria⩾3.5 g/day per 1.73 m2). Patients in the upper tertile for proteinuria differed from those with lower proteinuria in terms of total cholesterol levels (P<0.01), the proportion of diabetics (P<0.01) and supine active renin concentration (P= 0.02). They tended to have higher systolic blood pressure levels (P= 0.07), a lower frequency of contralateral renal artery stenosis (P= 0.09) and a longer contralateral kidney (P= 0.09). In multivariate logistic regression, the factors independently linked to proteinuria in the upper tertile were active renin concentration (P= 0.05) and contralateral kidney length (P= 0.02). Proteinuria significantly decreased in nephrotic patients (P<0.01) treated with revascularization or nephrectomy and/or angiotensin converting enzyme inhibition.ConclusionsProteinuria in renal artery occlusion is positively related to active renin concentration, which reflects plasma angiotensin II concentration. Therapy aimed at lowering angiotensin II levels decreased proteinuria in nephrotic patients. The positive relationship between proteinuria and contralateral kidney length may reflect compensatory hypertrophy in response to nephron function loss.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID